Neoadjuvant chemotherapy of node-positive M0 urothelial bladder cancer.

684 Background: Patients (pts) with muscle-invasive bladder cancer (MIBC) who are initially candidates for radical cystectomy (RC) benefit from the neoadjuvant chemotherapy (NACT) if they receive a multi-agent regimen containing cisplatin. Most clinical trials that established role of NACT excluded pts with suspicious or positive regional lymph nodes (cN1-N3; cN+), which were then considered stage IV, now corresponding to stage III in the TNM 8 th ed. classification. Current guidelines largely extrapolate existing therapeutic strategies for patients with cN+ disease, although persistent ypN+ disease after NACT followed by RC shows high relapse rates with limited survival outcomes. The study aims to analyze combined radical treatment in cN+ pts and a role of NACT regimen: gemcitabine and cisplatin (GC) vs dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (ddMVAC) in real medical practice. Methods: Pts with MIBC stage ≥T2 who underwent NACT ddMVAC or GC from 11/2016 to 05/2025 were included in the study. Pts from clinical trials and treated with other NACT regimens were excluded. Complete clinical data were collected from 7 polish cancer centers. Retrospective survival analysis was performed using the Kaplan-Meier method, and log-rank, chi-square, or Fisher's tests were used to compare groups. Data cut-off was 14/10/2025. Results: Of the 330 pts treated with at least one cycle of NACT, 293 were included in the analysis: 132 (45%) received ddMVAC, 161 (55%) received GC; 76 (26%) were women. The number of cN+ pts at baseline was 71 (24%). A total of 247 (84%) pts underwent RC. A statistically significant difference in overall survival (OS) and disease free survival (DFS) favoring ddMVAC in whole study cohort was demonstrated, HR, 0.58; 95% CI, 0.40–0.84; p = 0.0034 and HR, 0.57; 95% CI, 0.40–0.80; p = 0.0014, respectively. cN+ patients had a non-significantly worse OS (HR, 0.69; 95% CI, 0.46–1.02; p = 0.0758) and a statistically significant worse DFS (HR, 0.60; 95% CI, 0.42–0.88; p = 0.0144). There was no difference in OS between ddMVAC cN+ and ddMVAC cN- (p = 0.8726), but a statistically significant longer OS was observed for ddMVAC cN+ vs GC cN+ (HR, 0.19; 95% CI, 0.05–0.76; p = 0.0127). The number of pts with cN+ at baseline who achieved ypN0 (downstaging) after RC was 40 (16%) and 25 (10%) of pts with initially cN0 who were found to have ypN+ (upstaging). GC group had poorer performance status, more comorbidities, and lower baseline GFR that may have affected survival outcomes. Conclusions: The use of NACT with the ddMVAC regimen in patients with MIBC showed a statistically significant prolongation of OS compared to GC. This superiority seems to be confirmed in the cN+ subgroup, which may indicate a higher activity of the ddMVAC in a population with a potentially worse prognosis. Further studies comparing the efficacy of standard NACT and novel perioperative regimens need to be conducted.